P2X purinoceptor 3 (P2X3) (P2X3)

The P2X3 receptor is a ligand-gated ion channel activated by extracellular adenosine triphosphate (ATP), primarily expressed in small-to-medium diameter sensory neurons of the dorsal root, trigeminal, and nodose ganglia [1, 4, 6, 11]. It typically functions as a homotrimeric complex or as a heterotrimer in association with P2X2 subunits, playing a pivotal role in the transmission of nociceptive (pain) signals and the mediation of autonomic reflexes such as the cough reflex and bladder voiding [6, 11, 12, 13]. Under conditions of tissue injury or inflammation, excessive ATP release leads to the sensitization and overactivation of P2X3 receptors, contributing to the pathophysiology of chronic refractory cough and various chronic pain states [4, 9, 11, 16]. Therapeutic development has focused on selective P2X3 antagonists, such as gefapixant and camlipixant, which aim to block ATP-mediated signaling to alleviate symptoms [4, 12, 15, 16]. A significant clinical challenge is achieving high selectivity for the P2X3 homotrimer over the P2X2/3 heterotrimer, as the latter is involved in taste perception, and its inhibition often results in dysgeusia [7, 11, 12]. These receptors are also implicated in urological dysfunctions like overactive bladder and interstitial cystitis due to their role in sensing bladder distension [6, 8, 13]. Selective inhibition of P2X3 offers a novel approach to managing afferent hypersensitivity without the central nervous system side effects common to traditional analgesics [6, 9, 12].

Other names

P2RX3Purinergic receptor P2X 3ATP receptorP2X receptor subunit 3Purinoceptor P2X3

P2X3 receptor antagonist; Negative allosteric modulator